Structural basis for the nuclear export activity of Importin13

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• Importin13 (Imp13) functions as a bidirectional karyopherin, mediating both the import and export of cellular cargoes.
• Imp13 interacts with import cargoes like Mago-Y14 and Ubc9, and the export cargo translation initiation factor 1A (eIF1A).

Purpose of the Study:

• To elucidate the molecular mechanism by which Importin13 (Imp13) performs its dual role in cargo transport.
• To understand how Imp13 facilitates the export of translation initiation factor 1A (eIF1A).

Main Methods:

• Determined crystal structures of Imp13 in complex with RanGTP and eIF1A at 3.6 Å resolution.
• Obtained a 3.0 Å crystal structure of unbound Imp13 to reveal its conformational states.
• Performed in vivo experiments to validate Imp13's binding and export capabilities for eIF1A.

Main Results:

• The crystal structure shows eIF1A binding to the inner surface of the Imp13 C-terminal arch, adjacent to RanGTP, explaining export mechanism.
• The unbound Imp13 structure reveals an open conformation, crucial for releasing export cargoes in the cytoplasm.
• Demonstrated that Imp13 binds and exports eIF1A in vivo, confirming its essential role in this process.

Conclusions:

• Imp13's ability to bind both import and export cargoes is structurally explained.
• The open conformation of Imp13 is key to releasing export cargoes, completing the export pathway.
• Imp13 plays an essential, functionally validated role in the export of eIF1A.